Polyphenol-stabilized coacervates for enzyme-triggered drug delivery

Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.

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We did not report sex and gender because there are no known effects of these grouping on coagulation.
We did not report on race or ethnicity because there are no known effects of these grouping on coagulation.
Patients were greater than 18 years of age, of both male and female gender and from all available ethnic backgrounds.No blood will be collected in patients with ongoing clinical instability (i.e.clinically serious arrhythmias, unrelieved cardiac ischemia or hypotension).No exclusions will be made on gender or race and the study population will reflect the typical patient undergoing cardiac catheterization and EP studies which will include female patients as well minorities Subjects were recruited from patients in the cath lab.
Study approved by UCSD VA IRB #H170005.
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